Cytotoxic and apoptotic evaluations of marine bacteria isolated from brine-seawater interface of the Red Sea.

BACKGROUND: High salinity and temperature combined with presence of heavy metals and low oxygen renders deep-sea anoxic brines of the Red Sea as one of the most extreme environments on Earth. The ability to adapt and survive in these extreme environments makes inhabiting bacteria interesting candidates for the search of novel bioactive molecules. METHODS: Total 20 i.e. lipophilic (chloroform) and hydrophilic (70% ethanol) extracts of marine bacteria isolated from brine-seawater interface of the Red Sea were tested for cytotoxic and apoptotic activity against three human cancer cell lines, i.e. HeLa (cervical carcinoma), MCF-7 (Breast Adenocarcinoma) and DU145 (Prostate carcinoma). RESULTS: Among these, twelve extracts were found to be very active after 24 hours of treatment, which were further evaluated for their cytotoxic and apoptotic effects at 48 hr. The extracts from the isolates P1-37B and P3-37A (Halomonas) and P1-17B (Sulfitobacter) have been found to be the most potent against tested cancer cell lines. CONCLUSION: Overall, bacterial isolates from the Red Sea displayed promising results and can be explored further to find novel drug-like molecules. The cell line specific activity of the extracts may be attributed to the presence of different polarity compounds or the cancer type i.e. biological differences in cell lines and different mechanisms of action of programmed cell death prevalent in different cancer cell lines

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Physiological traits of the symbiotic bacterium Teredinibacter turnerae isolated from the mangrove shipworm Neoteredo reynei

Nutrition in the Teredinidae family of wood-boring mollusks is sustained by cellulolytic/nitrogen fixing symbiotic bacteria of the Teredinibacter clade. The mangrove Teredinidae Neoteredo reynei is popularly used in the treatment of infectious diseases in the north of Brazil. In the present work, the symbionts of N. reynei, which are strictly confined to the host's gills, were conclusively identified as Teredinibacter turnerae. Symbiont variants obtained in vitro were able to grow using casein as the sole carbon/nitrogen source and under reduced concentrations of NaCl. Furthermore, cellulose consumption in T. turnerae was clearly reduced under low salt concentrations. As a point of interest, we hereby report first hand that T. turnerae in fact exerts antibiotic activity. Furthermore, this activity was also affected by NaCl concentration. Finally, T. turnerae was able to inhibit the growth of Gram-negative and Gram-positive bacteria, this including strains of Sphingomonas sp., Stenotrophomonas maltophilia, Bacillus cereus and Staphylococcus sciuri. Our findings introduce new points of view on the ecology of T. turnerae, and suggest new biotechnological applications for this marine bacterium

Bacterial Community Profiling of Milk Samples as a Means to Understand Culture-Negative Bovine Clinical Mastitis

Inflammation and infection of bovine mammary glands, commonly known as mastitis, imposes significant losses each year in the dairy industry worldwide. While several different bacterial species have been identified as causative agents of mastitis, many clinical mastitis cases remain culture negative, even after enrichment for bacterial growth. To understand the basis for this increasingly common phenomenon, the composition of bacterial communities from milk samples was analyzed using culture independent pyrosequencing of amplicons of 16S ribosomal RNA genes (16S rDNA). Comparisons were made of the microbial community composition of culture negative milk samples from mastitic quarters with that of non-mastitic quarters from the same animals. Genomic DNA from culture-negative clinical and healthy quarter sample pairs was isolated, and amplicon libraries were prepared using indexed primers specific to the V1–V2 region of bacterial 16S rRNA genes and sequenced using the Roche 454 GS FLX with titanium chemistry. Evaluation of the taxonomic composition of these samples revealed significant differences in the microbiota in milk from mastitic and healthy quarters. Statistical analysis identified seven bacterial genera that may be mainly responsible for the observed microbial community differences between mastitic and healthy quarters. Collectively, these results provide evidence that cases of culture negative mastitis can be associated with bacterial species that may be present below culture detection thresholds used here. The application of culture-independent bacterial community profiling represents a powerful approach to understand long-standing questions in animal health and disease

Pemphigus autoimmunity: Hypotheses and realities

The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients

Measurement of the low-energy antitriton inelastic cross section

In this Letter, the first measurement of the inelastic cross section for antitriton–nucleus interactions is reported, covering the momentum range of 0.8 ≤ p < 2.4 GeV/c. The measurement is carried out using data recorded with the ALICE detector in pp and Pb–Pb collisions at a centre-of-mass energy per nucleon of 13 TeV and 5.02 TeV, respectively. The detector material serves as an absorber for antitriton nuclei. The raw yield of (anti)triton nuclei measured with the ALICE apparatus is compared to the results from detailed ALICE simulations based on the GEANT4 toolkit for the propagation of (anti)particles through matter, allowing one to quantify the inelastic interaction probability in the detector material. This analysis complements the measurement of the inelastic cross section of antinuclei up to A=3 carried out by the ALICE Collaboration, and demonstrates the feasibility of the study of the isospin dependence of inelastic interaction cross section with the analysis techniques presented in this Letter

Modification of charged-particle jets in event-shape engineered Pb-Pb collisions at √SNN=5.02 TeV

Charged-particle jet yields have been measured in semicentral Pb–Pb collisions at center-of-mass energy per nucleon–nucleon collision sNN=5.02 TeV with the ALICE detector at the LHC. These yields are reported as a function of the jet transverse momentum, and further classified by their angle with respect to the event plane and the event shape, characterized by ellipticity, in an effort to study the path-length dependence of jet quenching. Jets were reconstructed at midrapidity from charged-particle tracks using the anti-kT algorithm with resolution parameters R = 0.2 and 0.4, with event-plane angle and event-shape values determined using information from forward scintillating detectors. The results presented in this letter show that, in semicentral Pb–Pb collisions, there is no significant difference between jet yields in predominantly isotropic and elliptical events. However, out-of-plane jets are observed to be more suppressed than in-plane jets. Further, this relative suppression is greater for low transverse momentum (&lt; 50 GeV/c) R = 0.2 jets produced in elliptical events, with out-of-plane to in-plane jet-yield ratios varying up to 5.2σ between different event-shape classes. These results agree with previous studies indicating that jets experience azimuthally anisotropic suppression when traversing the QGP medium, and can provide additional constraints on the path-length dependence of jet energy loss

Towards the understanding of the genuine three-body interaction for p–p–p and p–p–Λ\Lambda

Three-body nuclear forces play an important role in the structure of nuclei and hypernuclei and are also incor- porated in models to describe the dynamics of dense baryonic matter, such as in neutron stars. So far, only indirect mea- surements anchored to the binding energies of nuclei can be used to constrain the three-nucleon force, and if hyperons are considered, the scarce data on hypernuclei impose only weak constraints on the three-body forces. In this work, we present the first direct measurement of the p–p–p and p–p–Lambda systems in terms of three-particle correlation functions car- ried out for pp collisions at √s = 13 TeV. Three-particle cumulants are extracted from the correlation functions by applying the Kubo formalism, where the three-particle inter- action contribution to these correlations can be isolated after subtracting the known two-body interaction terms. A nega- tive cumulant is found for the p–p–p system, hinting to the presence of a residual three-body effect while for p–p–Lambda the cumulant is consistent with zero. This measurement demon- strates the accessibility of three-baryon correlations at the LHC

Observation of abnormal suppression of f0(980) production in p-Pb collisions at √sNN=5.02 TeV

The dependence of f0(980) production on the final-state charged-particle multiplicity in p–Pb collisions at sNN=5.02 TeV is reported. The production of f0(980) is measured with the ALICE detector via the f0(980)→π+π− decay channel in a midrapidity region of −0.5&lt;0. Particle yield ratios of f0(980) to π and K⁎(892)0 are found to be decreasing with increasing charged-particle multiplicity. The magnitude of the suppression of the f0(980)/π and f0(980)/K⁎(892)0 yield ratios is found to be dependent on the transverse momentum pT, suggesting different mechanisms responsible for the measured effects. Furthermore, the nuclear modification factor QpPb of f0(980) is measured in various multiplicity ranges. The QpPb shows a strong suppression of the f0(980) production in the pT region up to about 4 GeV/c. The results on the particle yield ratios and QpPb for f0(980) may help to understand the late hadronic phase in p–Pb collisions and the nature of the internal structure of f0(980) particle